Effects of tocainide on normal and myotonic mammalian skeletal muscle

The effects of the lidocaine derivative 2-amino-2',6'-propionoxylidide hydrochloride (tocainide, W-36095) on the contraction force and on membrane resting and action potentials of rat diaphragm were tested in vitro. In a concentration of 5 x 10(-4) mol/l, tocainide reduced the amplitude of the twitch by about 25% within 15 min. This reduction was reversible on washout of the drug. Tocainide had little effect on the membrane resting potential, but considerably affected the action potential: rate of rise, maximum amplitude and rate of fall were reduced, the duration increased. The conduction velocity of the action potential was reduced by 20%. Experimental myotonia produced in excised diaphragms or in anesthetized whole animals by anthracene-9-carboxylic acid was completely abolished by low doses of tocainide.